The complete structure determination of slow reacting substance of anaphylaxis (SRS-A) which has been implicated as a chemical mediator of the immunologically produced bronchospasm in asthma is proposed in the following research. High resolution mass spectrometry and field desorption ionization techniques will be applied to the structural studies of SRS-A. Techniques suitable for quantitative analysis of SRS-A will be developed based on high pressure liquid chromatography and mass spctrometry. A model system for SRS-S to be further explored is slow reacting substances produced by the incubation of the calcium ionophore A23187 with mouse mastocytoma cells and rat peritoneal cells. A purification procedure utilizing reversed phase high pressure liquid chromatography has been developed and will be refined which provides essentially pure SRS. Already it has revealed the presences of separable and therefore, structurally different species SRS in one model system which can be defined as SRS by bioassay. One SRS has been structurally identified by chemical degradation and mass spectrometric procedures as 6-cysteinyl-5-hydroxy-7,9,11,14-eicosatetraenoic acid. This molecule is a member of a series of compounds generated by a novel lipoxygenase pathway of arachidonic acid metabolism and we have named the members of this family leukotrienes. Studies of the further biochemical metabolism of leukotriene-C (LT-C) using radiolabeled material and mass spectral analysis will be carried out. Using specific chemical assays for SRS (LT-C) and its metabolites, manipulation of the biochemical pathways of SRS synthesis and metabolism through pharmacologic means will be investigated. Such studies are hoped to provide basic information for an eventual rational approach to therapy for certain forms of bronchial asthma as well as a better understanding of the physiological role of leukotrienes.